Menin inhibitors for patients with relapsed/refractory acute myeloid leukemia (AML): a systematic review and...

Menin inhibitors (MI) are promising targeted therapies for acute myeloid leukemia (AML), particularly in NPM1-mutated and KMT2A-rearranged disease. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of MI-based therapy in adults with relapsed/refractory AML. A search of six databases through January 2026 identified 14 studies including 784 treated patients. Among response-evaluable cohorts (k = 22; n = 579), the pooled overall response rate (ORR) was 54.6% (95% CI 46.4-62.6; I²=63.5%). The pooled complete response (CR) rate was 29.3%, and CR+CRh was 28.5%. Combination therapy with MI plus hypomethylating agent and venetoclax produced higher CR (43.3% vs 19.5%; p = 0.002) and CR+CRh rates (48.6% vs 25.8%; p = 0.007) than monotherapy. Common adverse events included LFT elevation (38.7%), febrile neutropenia (33.6%), and diarrhea (28.8%). Differentiation syndrome occurred in 14.6%, and treatment-related mortality in 5.0%. MI-based therapy demonstrates meaningful activity in heavily pretreated AML, with deeper responses observed using combination strategies.